Toxicological evaluation of some food
    additives including anticaking agents,
    antimicrobials, antioxidants, emulsifiers
    and thickening agents


    The evaluations contained in this publication
    were prepared by the Joint FAO/WHO Expert
    Committee on Food Additives which met in Geneva,
    25 June - 4 July 19731

    World Health Organization


    1    Seventeenth Report of the Joint FAO/WHO Expert Committee on
    Food Additives, Wld Hlth Org. techn. Rep. Ser., 1974, No. 539;
    FAO Nutrition Meetings Report Series, 1974, No. 53.



         This substance has been evaluated for acceptable daily intake by
    the Joint FAO/WHO Expert Committee on Food Additives (see Annex 1,
    Ref. No. 23) in 1970.

         Since the previous evaluation, additional data have become
    available and are summarized and discussed in the following monograph.
    The previously published monograph has been expanded and is reproduced
    in its entirety below.



         Mineral oils are of variable composition depending on the boiling
    point of the fractions used. For food purposes usually liquid
    petrolatum or liquid paraffin are employed which consist essentially
    of n-alkanes and some cyclic paraffins. They are chemically inert
    especially as regards the straight chain alkanes and on ingestion most
    of the mineral oil (98%) remains unabsorbed in the faeces. There is
    evidence now that small amounts of mineral oil (2%) are absorbed as
    such by the intestinal mucosa and are distributed throughout the body.
    A very small fraction may undergo further biochemical transformation.
    Sources of mineral oil are laxatives or oils used in food technology
    as release agents or for lubrication purposes (Boitnott & Margolis,

         Oil droplets, identified as saturated alkane hydrocarbons, have
    been demonstrated in mesenteric lymphnodes and nodes of the porta
    hepatis in man. Similar droplets have been identified in human liver,
    spleen and adipose tissue. The small amounts formed are consistent
    with the calculated intake from food use (47.5 per head per year in
    the United States of America). The quantities of extractable oil and
    types of histological appearance have been reported (Boitnott &
    Margolis, 1970). There is no correlation with age or sex (Kelsall &
    Blackwell, 1969). There is an unusual geographical incidence, being
    about 50% in North America and 10% in Western Europe and in post
    mortem examinations (Cruikshank, 1972). No known harm appears
    associated with these residues (Boitnott & Margolis, 1966).

         Similar deposition of oil and minor absorption was demonstrated
    in rabbits, rats and guinea-pigs fed liquid petrolatum for seven
    months or more. Histochemical evidence showed absorption to be
    proportionate to length of exposure. The mechanism of absorption was
    unknown but the absorbed particles showed evidence of foreign body
    reaction and phagocytic ingestion (Stryker, 1941).

         Mineral oil used as emulsifying medium for s.c. injection was
    transported from the site of injection without causing any systemic
    effects (Brown, 1966).

         H3-labelled mineral oil was administered to rats orally and i.p.
    five hours after oral dosing with 0.66 mg/kg bw it could be shown 
    that over 80% was not absorbed but excreted in the faeces, 1-5%
    was absorbed unchanged and another 15% appeared in carcass as H3
    non-mineral oil substance. Some H3 had exchanged with available
    H and possibly some mineral oil had been modified metabolically.
    Radioactivity was found principally in liver, fat, kidney, brain, and
    spleen. Following i.p. administration there was only very slow
    excretion. 11% appeared in the faeces during eight days and only
    traces in the urine (Ebert et al., 1966).

         Mineral oil passes through the gut wall unchanged and more is
    absorbed in the presence of powerful emulsifiers, provided that the
    particle size of the emulsion is about 0.5 µ (Frazer et al., 1944).
    Prolonged administration of 0.66 ml/kg for 31 days had no effect on
    the amount absorbed when compared with single dosing (Ebert et al.,

         A wide range of fractions of mineral oil contain carcinogenic
    compounds especially higher boiling fractions of the range
    300°-350°-400°C as shown by skin painting of mice and rabbits (Cook et
    al., 1958) but refined material may be free from these carcinogenic
    constituents (Prigal, 1967). Inoculation of 64 mice with a combination
    of mineral oil and killed staphylococci induced plasma cell tumours in
    seven animals (Potter & Robertson, 1961). Later experiments produced
    similar results with mineral oil alone (Potter & Boyce, 1962). Some
    doubts have been raised as to the probable role of virus in production
    of these mouse plasma cell tumours (Prigal, 1967). No human cancer has
    been reported following many years of oleothorax use (Prigal, 1967).

         Work is going on on the metabolism of n-alkanes (heptadecane,
    C17, eicosane, C20, - tetracosane, C24, and dotriacontane, C32), one
    isoparaffin ((CH3)7nonane; C16) and one cycloparaffin
    (dodecylcyclohexane; C18) in rat. The preliminary results are
    summarized in the following table.



    n-alkane/  (CH3)7-   Dodecyl-
    Days       nonane    cyclohexane  Heptadecane   Eicosane   Tetracosane
               (C16)     (C18)        (n-C17)       (n-C20)    (n-C24)

    1          0.21      1.66         1.46          3.87       22.43

    2          0.24      1.20         5.02          1.53       1.83

    3          2.63      3.07         0.10          0.10       0.46

    4          0         0            0             0          0.08

    5          -         -            -             -          0.02

    6          -         -            -             -          0

    Total      3.08      5.93         6.58          5.50       24.82

         No urine excretion was observed.

         Some points have been noted:

         (a)  The isoparaffin is absent in the carcass.

         (b)  0.8% of the ingested dose of tetracosane (C24) is retained.

         (c)  For the other n-alkanes, between 7 and 10% of the ingested
              dose are retained after 21 days. This is equivalent to 7 ppm
              (0.0007%) in the carcass.

         Heptadecane and dodecylcyclohexane were given, during one week, 
    to eight rats at a daily dose of 15 mg incorporated in the diet.  At
    day 10, the animals were sacrificed. The following levels were  found
    in the organs or tissues: liver 2.5 ppm (0.00025%); spleen 1.5 ppm
    (0.00015%); lung 2.3 ppm (0.00023%); heart 0.5 ppm (0.00005%); muscle
    34 ppm (0.0034%); adipose tissue 317 ppm (0.0317%) (Tulliez & Bories,

         Traces (0.001-0.1%) of n-alkanes (C17 to C31) are found normally
    in plants. Protein sources from Spirula family algae contain up to
    0.15% heptadecane.


    Special studies

    Nutritional implications

         There are two possible reasons for the presence of mineral oil in
    food; (1) in trace amounts from its use as a lubricant or separant
    e.g. in tin-greasing before baking, or from traces on the surface of
    knives used to cut dough in breadmaking, or as a coating e.g. of
    fruit; (2) as a substitute for fat either because it is cheaper or in
    slimming foods. The maximum daily intake is calculated to be about
    100 mg of which some 80 mg are contributed from its use on the
    machinery in the baking industry (Council on White Mineral Oil, 1961).

         There has been a great deal of work on the effect of mineral oil
    in impeding the absorption of fat soluble vitamins A (and precursors)
    D. E. K. and essential fatty acids. There is no doubt that
    interference with absorption can occur, particularly of carotene if
    amounts in food exceed approximately 6000 ppm (Steigmann et al.,
    1952). Whether the amounts likely to appear in the food of children
    are of clinical importance is much less certain (assuming that it is
    not used as an ingredient as in (2) above). But the diets of many of
    these may contain amounts of these vitamins that are in any case
    marginal or inadequate and there seems no reason for the inclusion of
    mineral oil in foods which are specifically intended for infants with
    the possible exception of rusks (concerning which inquiries are being
    made which will be later reported as they may be subject to the same
    contaminating processes as bread).

    Short-term studies


         Ten rats were each fed a total of 17 g liquid paraffin in 18 g
    olive oil over 16 days mixed into their normal diet. Some 65% was
    absorbed as estimated from faecal loss. Another five rats received
    over 28 days a total of 28 g liquid paraffin in their diet. Only 9%
    was absorbed. Lymph collected during absorption from intestinal
    lymphatics showed that absorbed paraffin had been metabolically
    modified (Daniel et al., 1953).


         Fifteen rabbits, weighing between 1.9 and 2.5 kg, were given
    daily 25 ml of a mixture (1:1) of olive oil and paraffin oil (purity
    not stated). The animals were sacrificed at regular intervals, after
    60-406 days of treatment. At this high dosage level, from the first to
    the third week, a relatively important loss of weight is noted, but
    rapidly a state comparable to the controls is regained. Progressively,

    the paraffin oil passes the intestinal epithelium and accumulates in
    the mesenteric lymph glands, then becoming distributed in the rest of
    the body, with preferential deposition in the liver and in the spleen.
    Histologically, diffuse hyperplasia of reticulo endothelial cells,
    somewhat similar to that seen in human Whipple's disease, is observed
    (Borer, 1960).

    Long-term studies


         Two groups of 30 mice had mineral oil applied to their skin three
    times weekly at 15 mg/application for 311 and 478 days respectively.
    No tumours were found (Esso Research, 1960).


         Animals were kept for 15 months on diets supplemented with 10%
    liquid paraffin. The liver contained 0.4% dry weight liquid paraffin.
    Some active metabolism may occur but liver function was not affected
    (Daniel et al., 1953). In another experiment 2% mineral oil was fed in
    the diet to 30 rats for 500 days without adverse effects (Schmähl &
    Reiter, 1953).


         The natural occurrence of hydrocarbons, particularly in food of
    plant origin, the use of food-grade mineral oil in food technology and
    the medicinal use of this material have resulted in detectable
    residues of mineral oil in human tissues. No pathological consequences
    seem to follow the retention of this material. Moreover, most of the
    ingested material is not absorbed but is excreted in the faeces.
    Nevertheless, such tissue storage is considered to be undesirable and
    exposure to food-grade mineral oil should be kept to a minimum.

         There are no other recognized toxicological problems arising from
    the present technological uses of food-grade mineral oil. Further work
    is desirable on the elucidation of the significance of stored mineral
    oil in the body. Recent technological progress results in production
    of mineral oil by hydrogenation. Such oils will contain more cyclic
    paraffin since aromatic components are not removed prior to
    distillation. No toxicological information is available on these newer


    Estimate of acceptable daily intake for man

         Not limited.*



         Elucidation of the significance of stored mineral oil in the


    Boitnott, J. K. & Margolis, S. (1966) Bull. Johns Hopk. Hosp., 118,

    Boitnott, J. K. & Margolis, S. (1970) Johns Hopkins Med. J., 127, 65

    Borer, F. (1960) Rev. franē. études clin. et biol., 5, 47

    Brown, E. A. (1966) Review of Allergy, 20, 148 & 235

    Cook, J. W., Carruthers, W. & Woodhouse, D. L. (1958) Brit. med.
         Bull., 14, 132

    Council on White Mineral Oil (1961) Food Additive Petition 302 to US
         Food and Drug Administration dated 21 February 1961

    Cruikshank, B. (1972) Personal communication

    Daniel, J. W. et al. (1953) Biochem. J., 54, 37

    Ebert, A. G., Schleifer, C. R. & Hess, S. M. (1966) J. Pharmac. Sci.,
         55, 923

    Esso Research (1960) Unpublished report submitted to WHO

    Frazer, A. C., Schulman, J. H. & Stewart, H. C. (1944) J. Physiol,
         103, 306


    *    See relevant paragraph in the seventeenth report, pp. 10-11.
    Applies only to mineral oil not made by hydrogenation process.

    Kelsall & Blackwell (1969) Pathology, 1, 211

    Potter, M. & Boyce, C. R. (1962) Nature, 193, 1086

    Potter, M. & Robertson, J. (1961) J. nat. Cancer Inst., 25, 847

    Prigal, S. J. (1967) Annals of Allergy, 25, 449

    Schmähl, D. & Reiter, A. (1953) Arzneimittel-Forsch., 3, 403

    Steigmann, F. et al. (1952) Gastroent., 20, 587

    Stryker, W. A. (1941) Arch. Pathol., 31, 670

    Tulliez, J. & Bories, G. (1973) Personal communication

    See Also:
       Toxicological Abbreviations
       Food-grade mineral oil (FAO Nutrition Meetings Report Series 48a)